Pulmonary macrophages are one of the sources of various antioxidant and detoxification enzymes for which NF-E2-related factor 2 (Nrf2) is a key transcriptional factor. Although Nrf2 deficiency reportedly induces severe emphysema in mice exposed to cigarette smoke (CS), no reports have studied Nrf2 regulation in chronic obstructive pulmonary disease (COPD). In this study, Nrf2 activation in response to CS was evaluated in human alveolar macrophages, and age-related differences in CS-induced Nrf2 regulation in mouse alveolar macrophages were determined. Furthermore, Nrf2 mRNA levels in human macrophages harvested by bronchoalveolar lavage or laser capture microdissection were measured. CS induced nuclear Nrf2 accumulation and up-regulation of Nrf2 target genes without substantial changes in Nrf2 mRNA levels in human alveolar macrophages. In humans, the Nrf2 mRNA level in lavaged macrophages of young subjects (n = 14) was independent of smoking status; however, the Nrf2 mRNA level was down-regulated in the lavaged macrophages of older current smokers (n = 14) compared with older nonsmokers (n = 9) (P < 0.001). Among older subjects, the macrophage Nrf2 mRNA level was inversely correlated with oxidized glutathione and carbonylated albumin levels in bronchoalveolar lavage fluid. In mice, aging suppressed the CS-induced up-regulation of Nrf2 target genes, as well as Nrf2, in alveolar macrophages. Furthermore, the Nrf2 mRNA level was decreased in laser capture microdissection-retrieved macrophages obtained from subjects with COPD (n = 10) compared with control subjects (n = 10) (P = 0.001). In conclusion, CS induces Nrf2 activation in macrophages, and Nrf2 expression is decreased in the macrophages of older current smokers and patients with COPD.

OBJECTIVE: Thrombus in the stump of the pulmonary vein (PV) is not a well-known complication after lung resection, and it has the potential to cause embolism to vital organs. To clarify the frequency, risk factors, and cause of this complication, a retrospective clinical study of patients who underwent lobectomy was performed.METHOD: The subjects were 193 patients with primary lung cancer who underwent lobectomy from 2005 to 2011 and contrast-enhanced chest CT within 2 years after lobectomy. Contrast-enhanced CT was retrospectively interpreted to check for thrombus in the PV stump.RESULTS: The operative procedures were 65 right upper lobectomies, 14 right middle lobectomies, 40 right lower lobectomies, 52 left upper lobectomies (LUL), and 22 left lower lobectomies. Of the 193 patients, 7 (3.6%) developed thrombus in the PV stump after lobectomy. All patients with thrombus had undergone LUL, and 13.5% of those who had undergone LUL developed thrombus. Univariate analyses revealed that LUL and operation time were significant risk factors, and that adjuvant chemotherapy was marginally significant. It appears that thrombus may be attributable to the length of the PV stump. Measurement of the length of the PV stump using three-dimensional CT images of the PV revealed that the stump of the left superior PV was longer than the others.CONCLUSION: Thrombus in the PV stump occurred in 13.5% of cases after LUL. These findings suggest that contrast-enhanced CT should be recommended for patients after LUL to help identify patients with a high risk for thromboembolism.(246 words)

A surgical specimen was obtained from a patient (female, 73 years old) who was diagnosed with lung adenocarcinoma (mixed subtypes) and underwent pulmonary lobe resection at the Department of Cardiovascular and Thoracic Surgery, Hokkaido University Hospital in 2015. The patient did not undergo any preoperative chemotherapy or radiotherapy. The resected lung cancer tissues (~1.0 cm 3 without necrosis) were put into ice-cold RPMI-1640 supplemented with 10% fetal bovine serum (HyClone, GE Healthcare), 0.1 mM non-essential amino acids (Gibco), 100 IU/ml penicillin and 100 μg/ml streptomycin (Gibco) and 0.03% glutamine (Gibco), and transported immediately to the lab. After the removal of blood clots, the sample was rinsed with sterile PBS and cut into small fragments (~1 mm 3

Background:We isolated tumour endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. No report is available on biglycan expression or function in TECs.Methods:The NEC and TEC were isolated. We investigated the biglycan expression and function in TECs. Western blotting analysis of biglycan was performed on sera from cancer patients.Results:Biglycan expression levels were higher in TECs than in NECs. Biglycan knockdown inhibited cell migration and caused morphological changes in TECs. Furthermore, immunostaining revealed strong biglycan expression in vivo in human tumour vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers.Conclusion:These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy.

BackgroundThrombosis in the left upper pulmonary vein stump after left upper lobectomy is a very rare but important complication because it occurs in the systemic circulation system. We previously made the first ever report on the frequency and risk factors of thrombosis in the pulmonary vein stump after lobectomy. In this study, we conducted an investigation in a different hospital to determine whether this was a common complication.MethodsFrom 2008 to 2012, 151 patients who underwent lobectomy and following enhanced CT within 2 years after the operation were studied. Postoperative contrast-enhanced CT imaging was retrospectively checked.ResultsWe found thrombosis in the pulmonary vein stump in 5 of the 151 patients (3.3%). All 5 patients underwent left upper lobectomy (17.9% of the patients who underwent left upper lobectomy). These 5 patients did not have infarction of any vital organ. The thrombus was disappeared several months later on contrast-enhanced CT in 3 patients and followed in 2 patients. On univariate analysis, there was a significant difference only in the operative procedure (p < 0.001).ConclusionsThrombosis in the pulmonary vein stump occurred with high frequency in patients who underwent left upper lobectomy. Because the frequency of thrombosis in this study was the same as in our previous report, this might be a common complication.